It is proposed that the invasion of eukaryotic cells by S. typhimurium consists of two consecutive phases. Initial attachment of the bacterium to the eukaryotic cell surface is followed by the second phase of penetration; the latter is possibly the result of bacterial substances inducing phagocytic activity of Hela cells. To delineate these phases it is necessary to use model systems with which adhesion can be studied separately from the overall process of invasion. Accordingly, adhesive properties will be investigated with isolated cytoplasmic membranes of eukaryotic cells, such as brush-border membranes and with 'inert' cells such as erythrocytes. Adhesive activities of salmonellae will be characterized and a quantitative assay method developed with these models. Invasive activity will be studied with an established system of Hela cell monolayers. The presence of bacterial products responsible for the induction of phagocytic activity in Hela cells will be investigated. Both non-adhesive and/or non-invasive strains are to be prepared; the test systems will be used to select mutants that lack either or both of these properties. The interdependence of adhesion and invasion will be investigated with these mutants. Substances responsible for the adhesive properties of salmonellae are to be isolated in a cell-free state and characterized; the test systems developed to assay adhesiveness of bacteria will be modified to detect cell-free adhesive substances. Likewise, the Hela cell model will be used to detect the existence of cell-free bacterial substances that induce Hela cells to engulf salmonellae (and other particles); such substances are to be characterized.